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XRCC1 polymorphisms associated with survival among Chinese bladder cancer patients receiving epirubicin and mitomycin C

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Tumor Biology

Abstract

The association between DNA repair gene polymorphisms and bladder cancer risk has been widely studied. However, only few studies have examined the correlation between bladder cancer and instillation agent sensitivity. The aim of this study was to examine the association between polymorphisms of DNA repair genes, namely X-ray repair cross-complementing group I (XRCC1) rs2854509 and rs3213255, and bladder cancer recurrence risk. We recruited 244 patients (130 treated with epirubicin and 114 treated with mitomycin C). Genomic DNA was used to examine the XRCC1 rs2854509 and rs3213255 genotypes by Taqman PCR analysis. Combination analysis of XRCC1 rs2854509 and rs3213255 and examination of XRCC1 diplotypes were performed to reveal possible correlations. The rs2854509 CC and rs3213255 TT genotypes conferred shorter survival times than the rs2854509 AC/AA and rs3213255 CC/CT genotypes in patients treated with epirubicin, but not in those treated with mitomycin C (MMC) in adjusted models [hazard ratio (HR) = 0.23, 95 % confidence interval (CI) = 0.10–0.53 for rs2854509 AC + AA compared with CC; HR = 0.17, 95 % CI = 0.06–0.46 for rs3213255 CC + CT compared with TT]. Combination analysis showed significantly increased recurrence-free survival (RFS) among patients simultaneously carrying the rs2854509 AC/AA and rs3213255 CC/CT genotypes with an HR of 0.15 (95 % CI = 0.05–0.45) compared to those carrying other genotypes. Diplotype analysis demonstrated that the A-C/C-T diplotype is associated with a lower risk of recurrence compared with the common wild C-T/C-T diplotype (HR = 0.17, 95 % CI = 0.06–0.51). Our results suggest that the rs2854509 CC and rs3213255 TT genotypes confer higher sensitivity to epirubicin instillation. Moreover, the A-C/C-T diplotype presents significantly lower recurrence risk than other diplotypes.

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References

  1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA 2014;64:9–29.

  2. Rubben H, Lutzeyer W, Fischer N, Deutz F, Lagrange W, Giani G. Natural history and treatment of low and high risk superficial bladder tumors. J Urol. 1988;139:283–5.

    CAS  PubMed  Google Scholar 

  3. Kaufman DS, Shipley WU, Feldman AS. Bladder cancer. Lancet. 2009;374:239–49.

    Article  CAS  PubMed  Google Scholar 

  4. Sant M, Allemani C, Santaquilani M, Knijn A, Marchesi F, Capocaccia R, et al. EUROCARE-4. Survival of cancer patients diagnosed in 1995–1999. Results and commentary. Eur J Cancer. 2009;45:931–91.

    Article  PubMed  Google Scholar 

  5. Alexandroff AB, Nicholson S, Patel PM, Jackson AM. Recent advances in bacillus Calmette-Guerin immunotherapy in bladder cancer. Immunotherapy. 2010;2:551–60.

    Article  CAS  PubMed  Google Scholar 

  6. Ali-el-Dein B, el-Baz M, Aly AN, Shamaa S, Ashamallah A. Intravesical epirubicin versus doxorubicin for superficial bladder tumors (stages pTa and pT1): a randomized prospective study. J Urol. 1997;158:68–73. discussion 73-64.

    Article  CAS  PubMed  Google Scholar 

  7. Sylvester RJ, Oosterlinck W, van der Meijden AP. A single immediate postoperative instillation of chemotherapy decreases the risk of recurrence in patients with stage Ta T1 bladder cancer: a meta-analysis of published results of randomized clinical trials. J Urol. 2004;171:2186–90. quiz 2435.

    Article  PubMed  Google Scholar 

  8. Przybylowska-Sygut K, Stanczyk M, Kusinska R, Kordek R, Majsterek I. Association of the Arg194Trp and the Arg399Gln polymorphisms of the XRCC1 gene with risk occurrence and the response to adjuvant therapy among polish women with breast cancer. Clin Breast Cancer. 2013;13:61–8.

    Article  CAS  PubMed  Google Scholar 

  9. Duell EJ, Wiencke JK, Cheng TJ, Varkonyi A, Zuo ZF, Ashok TD, et al. Polymorphisms in the DNA repair genes XRCC1 and ERCC2 and biomarkers of DNA damage in human blood mononuclear cells. Carcinogenesis. 2000;21:965–71.

    Article  CAS  PubMed  Google Scholar 

  10. Giachino DF, Ghio P, Regazzoni S, Mandrile G, Novello S, Selvaggi G, et al. Prospective assessment of XPD Lys751Gln and XRCC1 Arg399Gln single nucleotide polymorphisms in lung cancer. Clin Cancer Res. 2007;13:2876–81.

    Article  CAS  PubMed  Google Scholar 

  11. Tengstrom M, Mannermaa A, Kosma VM, Hirvonen A, Kataja V. XRCC1 rs25487 polymorphism predicts the survival of patients after postoperative radiotherapy and adjuvant chemotherapy for breast cancer. Anticancer Res. 2014;34:3031–7.

    CAS  PubMed  Google Scholar 

  12. Sacerdote C, Guarrera S, Ricceri F, Pardini B, Polidoro S, Allione A, et al. Polymorphisms in the XRCC1 gene modify survival of bladder cancer patients treated with chemotherapy. Int J Cancer. 2013;133:2004–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Hung RJ, Hall J, Brennan P, Boffetta P. Genetic polymorphisms in the base excision repair pathway and cancer risk: a huge review. Am J Epidemiol. 2005;162:925–42.

    Article  PubMed  Google Scholar 

  14. Arizono K, Osada Y, Kuroda Y. DNA repair gene hOGG1 codon 326 and XRCC1 codon 399 polymorphisms and bladder cancer risk in a Japanese population. Jpn J Clin Oncol. 2008;38:186–91.

    Article  PubMed  Google Scholar 

  15. Sakano S, Wada T, Matsumoto H, Sugiyama S, Inoue R, Eguchi S, et al. Single nucleotide polymorphisms in DNA repair genes might be prognostic factors in muscle-invasive bladder cancer patients treated with chemoradiotherapy. Br J Cancer. 2006;95:561–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Sanyal S, De Verdier PJ, Steineck G, Larsson P, Onelov E, Hemminki K, et al. Polymorphisms in XPD, XPC and the risk of death in patients with urinary bladder neoplasms. Acta Oncol. 2007;46:31–41.

    Article  CAS  PubMed  Google Scholar 

  17. Li C, Hu Z, Lu J, Liu Z, Wang LE, El-Naggar AK, et al. Genetic polymorphisms in DNA base-excision repair genes ADPRT, XRCC1, and APE1 and the risk of squamous cell carcinoma of the head and neck. Cancer. 2007;110:867–75.

    Article  CAS  PubMed  Google Scholar 

  18. Moreno V, Gemignani F, Landi S, Gioia-Patricola L, Chabrier A, Blanco I, et al. Polymorphisms in genes of nucleotide and base excision repair: risk and prognosis of colorectal cancer. Clin Cancer Res. 2006;12:2101–8.

    Article  CAS  PubMed  Google Scholar 

  19. Cullinane C, Cutts SM, Panousis C, Phillips DR. Interstrand cross-linking by adriamycin in nuclear and mitochondrial DNA of MCF-7 cells. Nucleic Acids Res. 2000;28:1019–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Memisoglu A, Samson L. Base excision repair in yeast and mammals. Mutat Res. 2000;451:39–51.

    Article  CAS  PubMed  Google Scholar 

  21. Watchko JF, Lin Z, Clark RH, Kelleher AS, Walker MW, Spitzer AR. Pediatrix Hyperbilirubinemia Study G. Complex multifactorial nature of significant hyperbilirubinemia in neonates. Pediatrics. 2009;124:e868–77.

    Article  PubMed  Google Scholar 

  22. Kaplan M, Renbaum P, Levy-Lahad E, Hammerman C, Lahad A, Beutler E. Gilbert syndrome and glucose-6-phosphate dehydrogenase deficiency: a dose-dependent genetic interaction crucial to neonatal hyperbilirubinemia. Proc Natl Acad Sci U S A. 1997;94:12128–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lu Q, Cui Y, Wu R. A multilocus likelihood approach to joint modeling of linkage, parental diplotype and gene order in a full-sib family. BMC Genet. 2004;5:20.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), the Program for Development of Innovative Research Team in the First Affiliated Hospital of Nanjing Medical University, Provincial Initiative Program for Excellency Disciplines of Jiangsu Province and the National Natural Science Foundation of China (grant numbers 81171963 and 81201571).

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    Authors and Affiliations

    1. Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, 210029, Nanjing, China

      Xiaheng Deng, Xiaolei Zhang, Yidong Cheng, Xiao Yang, Ruizhe Zhao, Xuzhong Liu, Xiao Li, Chao Qin, Qiang Lu & Changjun Yin

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    1. Xiaheng Deng
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    2. Xiaolei Zhang
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    3. Yidong Cheng
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    Correspondence to Qiang Lu.

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    Xiaheng Deng, Xiaolei Zhang and Yidong Cheng contributed equally to this work.

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    Deng, X., Zhang, X., Cheng, Y. et al. XRCC1 polymorphisms associated with survival among Chinese bladder cancer patients receiving epirubicin and mitomycin C. Tumor Biol. 36, 4591–4596 (2015). https://doi.org/10.1007/s13277-015-3104-0

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    • DOI: https://doi.org/10.1007/s13277-015-3104-0

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